The main structural elements of bone are osteoid, which is a protein matrix, and hydroxyapatite (calcium phosphate) crystals, which are embedded in the osteoid. The major functional cells are osteoclasts, which resorb old bone, and osteoblasts, which form new bone.
Osteoporosis is a condition in which the bones become so weak and brittle that even mild stresses can cause a fracture. Both hydroxyapatite and osteoid are reduced proportionately in osteoporotic bone.
Non-modifiable: age, race (Caucasian, Asian), female gender, early menopause (<45years old), slender build (<57kgs), positive family history.
Modifiable: low calcium intake, low vitamin D intake, estrogen (female hormone) deficiency, sedentary lifestyle, cigarette smoking, alcohol excess (>2 drinks/day), caffeine excess (>2 servings/day), medications (glucocorticoids, excess thyroxine).
Women of age more than 65 years or older
Postmenopausal women who are below 65 years
Women considering therapy for osteoporosis
Women on hormone replacement therapy for a longer time
Standard radiographs are inadequate for accurate bone mass assessment. The most accurate and widely used methods in current practice are dual-energy x-ray absorptiometry (DEXA), computed tomography (CT), ultrasound (US). In my opinion, DEXA offers the best accuracy and precision with the least radiation exposure in most patients. Radiation exposure is 2 uSv per site (a chest X-ray is 100uSv).
Spine and hip densitometry (central densitometry) measurements are the best predictors of fracture risk and have the best precision for longitudinal monitoring. Peripheral densitometry measurements (heel, radius, hands) are available easily and are less expensive.
Densitometry values can vary greatly in the same individual at different skeletal sites. Therefore, even when peripheral bone densitometry values are normal, follow up central densitometry must still be considered in the following circumstances:
History of fragility fractures.
Two or more risk factors for bone loss.
Medical conditions associated with bone loss.
Medications that cause bone loss
Postmenopausal women not on HRTs, who would consider treatment if bone density is low.
The most useful values on the bone densitometry report are the T- score, Z-score, and absolute bone densitometry (BMD).
T score: It is a comparison of the patient’s bone mass to the young normal subjects (age 30). The T-score is the number of standard deviations (SDs) the patient’s value is below or above the mean value for young normal subjects (peak bone mass). A T score of -2 determines that the patient's bone mass is 2 SDs below normal. The T score indicates whether or not the patient has osteoporosis.
Z-score: It is a comparison of the patient’s bone mass to the age-matched subjects. The Z- the score determines whether or not the patient’s bone mass is appropriate for age or whether other factors are likely to account for excessively low bone mass. The Z-score is the number of SDs the patient’s value is below or above the mean value for age-matched normal subjects.
Absolute BMD: The actual bone density value is expressed in g/cm2 and it is the best parameter to use for calculation of per cent changes in BMD during longitudinal follow up.
It is made when a patient has a characteristic osteoporotic fracture or when the T-score on the bone densitometry is sufficiently low. The World Health Organization criteria for T-score interpretation are as follows.
T -score >-1: Normal.
T-score between -1 and -2.5: Osteopenia.
T-score <-2.5: Osteoporosis.
T-score of less than -2.5 makes a diagnosis of osteoporosis even in the absence of a fracture. Before concluding that reduced bone mass or a fracture is due to osteoporosis, one must first rule out other causes of low bone mass.
|T-score||% Bone Loss*||Fracture risk†|
|-1||12%||2 times increased|
*note that one has to lose 30% of bone mineral density to see osteopenia on routine radiographs.
†if a person has had a previous fragility fracture, the risk of subsequent fracture doubles again, i.e., if T-score was -3, fracture risk is 2 X 8=16.
The WHO diagnostic criteria apply only to postmenopausal white women.
Disparities exist among bone density values at different sites and with different methods.
Low bone mass does not necessarily indicate an ongoing bone loss.
Low bone mass is not always osteoporosis.
Bone densitometry cannot differentiate among the causes of low bone mass.
A complete history and physical examination is the first step in evaluation. Apart from this complete blood count with erythrocyte sedimentation rate, serum calcium, phosphorus, alkaline phosphatase, creatinine, CO2, chloride, serum TSH, serum testosterone (men), 24 hr urine calcium, and creatinine.
The proper amount of calcium intake is 1000mg/day for premenopausal women and men. 1500mg/day for postmenopausal women and men more than 65 years of age.
Adequate Vitamin D intake: 400-800 units/day.
Adequate exercise: aerobic and resistance.
Limiting alcohol consumption to 2 drinks a day or less.
Limiting caffeine consumption to 2 servings a day or less.
The major bioavailable sources of calcium are dietary products and calcium-fortified drinks. Their calcium content approximately is given below:
Milk- 300mg/cup (8oz).
Fruit juice with calcium- 300mg/cup (8oz).
Total these amounts plus 300mg for the general non-dairy diet and you have a reasonable estimate of your daily dietary calcium intake.
How can I ensure an adequate intake of calcium and vitamin D? What is the best calcium supplement?
A person absorbs only one-third of the calcium he or she ingests. Low-fat dairy products are best to increase calcium intake without increasing the risk of kidney stones. You should judge your calcium intake as per the contents of calcium in various dairy products which are mentioned above. Any shot falls in dietary calcium intake should be supplemented with calcium tablets, elixirs, or multivitamins. Multivitamins contain 400 units of vitamin D per tablet; one or two tablets per day are sufficient for most patients.
Patients who require calcium supplements above their diet to reach adequate daily calcium intake should take either calcium carbonate or calcium citrate. Calcium carbonate is less expensive but needs acidification for best absorption. Because of the acid buffering capacity of the calcium carbonate, it should be taken with meals and in a split dose of no more than 500-1000mg per dose (e.g.500mg thrice daily). Calcium citrate may be better alternative inpatient with achlorhydria or on medications to limit acid in the stomach.
It is important to make sure how much elemental calcium is in each pill. To determine whether a particular calcium supplement will be absorbed, put one pill in a glass of vinegar and see if it is dissolved in 30 minutes. If not, it isn’t being absorbed.
Patients who develop constipation due to calcium should take a calcium/magnesium preparation since the magnesium may stimulate gut motility.
Bone-resorption inhibiting agents such as estrogen, bisphosphonates, raloxifene, calcitonin.
Bone-formation stimulating agents such as fluoride, androgens, growth hormone, parathyroid hormone.
The non-pharmacologic measures are appropriate for all individuals who want to reduce the risk of developing osteoporosis. The national osteoporotic foundation further recommends that pharmacologic therapy be initiated in any patient who has T-score of -2.0 or less and in patients with a T-score of -1.5 or less in the presence of other osteoporotic risk fractures.
Measurement of the level of N-telopeptides (NTX) in the urine provides an estimate of the activity of bone turnover. NTX is a breakdown product of type 1 collagen in the bone. A 24hr urine or second voided morning spot urine can be used. There is a 15% average difference between the value obtained between these methods of urine collection. A normal urine NTX is a 20-65 BCE/mmol Cr. However, a value greater 50 predicts a loss of BMD over the next year while a value between 2.0 and 35 represents good control on present therapy.
Because of the precision error of a central DEXA scan, a change of ≥ 3% in the spine and ≥ 6% in the femur is considered significant. Osteophytes, vertebral fractures, and aortic calcification can falsely increase values in the spine. Hip malposition and including the ischium in the field of measurement can affect femur position.
GC therapy in supraphysiologic doses (prednisolone >7mg/dl) has several detrimental effects on the bone. First, they directly inhibit osteoblastic bone formation. Second, they impair intestinal calcium absorption and promote renal calcium excretion, thereby lowering serum calcium levels sufficiently to increase the secretion of parathyroid hormone (PTH), which then stimulates bone resorption. They also impair secretion of gonadal steroids, which further increase bone resorption.
Non-pharmacologic measures are indicated in all patients taking GCs. Pharmacological interventions should be considered for patients who will be on 7.5 mg/day of prednisone (or an equivalent dose of another GC) for at least 3months, particularly in postmenopausal women and in any individuals who have T-scores of -1 or less or who have fragility fractures.
Patients on GC therapy should take calcium (1500mg/day) and vitamin D (800 units/day). If urinary calcium excretion exceeds 300mg/day, a thiazide diuretic may be added. Most of the bisphosphonates are useful in GIOP. Calcitonin can be used, but its effects are less than that of bisphosphonates. Patients with decreased function of gonads should receive gonad steroid replacements.
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